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  1. Article ; Online: Mechanochemical Signaling Directs Cell-Shape Change.

    Schiffhauer, Eric S / Robinson, Douglas N

    Biophysical journal

    2017  Volume 112, Issue 2, Page(s) 207–214

    Abstract: ... of cell-shape changes is the ability of the cell's machinery to sense mechanical forces and tune the force ...

    Abstract For specialized cell function, as well as active cell behaviors such as division, migration, and tissue development, cells must undergo dynamic changes in shape. To complete these processes, cells integrate chemical and mechanical signals to direct force production. This mechanochemical integration allows for the rapid production and adaptation of leading-edge machinery in migrating cells, the invasion of one cell into another during cell-cell fusion, and the force-feedback loops that ensure robust cytokinesis. A quantitative understanding of cell mechanics coupled with protein dynamics has allowed us to account for furrow ingression during cytokinesis, a model cell-shape-change process. At the core of cell-shape changes is the ability of the cell's machinery to sense mechanical forces and tune the force-generating machinery as needed. Force-sensitive cytoskeletal proteins, including myosin II motors and actin cross-linkers such as α-actinin and filamin, accumulate in response to internally generated and externally imposed mechanical stresses, endowing the cell with the ability to discern and respond to mechanical cues. The physical theory behind how these proteins display mechanosensitive accumulation has allowed us to predict paralog-specific behaviors of different cross-linking proteins and identify a zone of optimal actin-binding affinity that allows for mechanical stress-induced protein accumulation. These molecular mechanisms coupled with the mechanical feedback systems ensure robust shape changes, but if they go awry, they are poised to promote disease states such as cancer cell metastasis and loss of tissue integrity.
    MeSH term(s) Animals ; Cell Shape ; Mechanotransduction, Cellular
    Language English
    Publishing date 2017-01-24
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 218078-9
    ISSN 1542-0086 ; 0006-3495
    ISSN (online) 1542-0086
    ISSN 0006-3495
    DOI 10.1016/j.bpj.2016.12.015
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Myosin IIB assembly state determines its mechanosensitive dynamics.

    Schiffhauer, Eric S / Ren, Yixin / Iglesias, Vicente A / Kothari, Priyanka / Iglesias, Pablo A / Robinson, Douglas N

    The Journal of cell biology

    2019  Volume 218, Issue 3, Page(s) 895–908

    Abstract: ... to chemical and mechanical inputs. Myosin IIs are key players in the cell's ability to react to mechanical ...

    Abstract Dynamical cell shape changes require a highly sensitive cellular system that can respond to chemical and mechanical inputs. Myosin IIs are key players in the cell's ability to react to mechanical inputs, demonstrating an ability to accumulate in response to applied stress. Here, we show that inputs that influence the ability of myosin II to assemble into filaments impact the ability of myosin to respond to stress in a predictable manner. Using mathematical modeling for
    MeSH term(s) Animals ; Dictyostelium/genetics ; Dictyostelium/metabolism ; HeLa Cells ; Humans ; Jurkat Cells ; Mechanotransduction, Cellular ; Mice ; Models, Biological ; NIH 3T3 Cells ; Nonmuscle Myosin Type IIB/genetics ; Nonmuscle Myosin Type IIB/metabolism ; Protein Kinase C/genetics ; Protein Kinase C/metabolism ; Protozoan Proteins/genetics ; Protozoan Proteins/metabolism
    Chemical Substances Protozoan Proteins ; protein kinase C zeta (EC 2.7.11.1) ; Protein Kinase C (EC 2.7.11.13) ; Nonmuscle Myosin Type IIB (EC 3.6.1.-)
    Language English
    Publishing date 2019-01-17
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 218154-x
    ISSN 1540-8140 ; 0021-9525
    ISSN (online) 1540-8140
    ISSN 0021-9525
    DOI 10.1083/jcb.201806058
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Parallel Compression Is a Fast Low-Cost Assay for the High-Throughput Screening of Mechanosensory Cytoskeletal Proteins in Cells.

    Miao, Chunguang / Schiffhauer, Eric S / Okeke, Evelyn I / Robinson, Douglas N / Luo, Tianzhi

    ACS applied materials & interfaces

    2017  Volume 9, Issue 34, Page(s) 28168–28179

    Abstract: ... theories, we simulated the mechanosensory accumulation of myosin II's and quantitatively reproduced ...

    Abstract Cellular mechanosensing is critical for many biological processes, including cell differentiation, proliferation, migration, and tissue morphogenesis. The actin cytoskeletal proteins play important roles in cellular mechanosensing. Many techniques have been used to investigate the mechanosensory behaviors of these proteins. However, a fast, low-cost assay for the quantitative characterization of these proteins is still lacking. Here, we demonstrate that compression assay using agarose overlay is suitable for the high throughput screening of mechanosensory proteins in live cells while requiring minimal experimental setup. We used several well-studied myosin II mutants to assess the compression assay. On the basis of elasticity theories, we simulated the mechanosensory accumulation of myosin II's and quantitatively reproduced the experimentally observed protein dynamics. Combining the compression assay with confocal microscopy, we monitored the polarization of myosin II oligomers at the subcellular level. The polarization was dependent on the ratio of the two principal strains of the cellular deformations. Finally, we demonstrated that this technique could be used on the investigation of other mechanosensory proteins.
    MeSH term(s) Actin Cytoskeleton ; Cytoskeletal Proteins/analysis ; Mechanotransduction, Cellular
    Chemical Substances Cytoskeletal Proteins
    Language English
    Publishing date 2017-08-21
    Publishing country United States
    Document type Journal Article
    ISSN 1944-8252
    ISSN (online) 1944-8252
    DOI 10.1021/acsami.7b04622
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Mechanoaccumulative Elements of the Mammalian Actin Cytoskeleton.

    Schiffhauer, Eric S / Luo, Tianzhi / Mohan, Krithika / Srivastava, Vasudha / Qian, Xuyu / Griffis, Eric R / Iglesias, Pablo A / Robinson, Douglas N

    Current biology : CB

    2016  Volume 26, Issue 11, Page(s) 1473–1479

    Abstract: ... catenin in adherens junctions [10] and vinculin's molecular clutch mechanism in focal adhesions [11 ... these mechanoaccumulative mechanisms drive the cell's response to physical perturbation during proper tissue development and ...

    Abstract To change shape, divide, form junctions, and migrate, cells reorganize their cytoskeletons in response to changing mechanical environments [1-4]. Actin cytoskeletal elements, including myosin II motors and actin crosslinkers, structurally remodel and activate signaling pathways in response to imposed stresses [5-9]. Recent studies demonstrate the importance of force-dependent structural rearrangement of α-catenin in adherens junctions [10] and vinculin's molecular clutch mechanism in focal adhesions [11]. However, the complete landscape of cytoskeletal mechanoresponsive proteins and the mechanisms by which these elements sense and respond to force remain to be elucidated. To find mechanosensitive elements in mammalian cells, we examined protein relocalization in response to controlled external stresses applied to individual cells. Here, we show that non-muscle myosin II, α-actinin, and filamin accumulate to mechanically stressed regions in cells from diverse lineages. Using reaction-diffusion models for force-sensitive binding, we successfully predicted which mammalian α-actinin and filamin paralogs would be mechanoaccumulative. Furthermore, a "Goldilocks zone" must exist for each protein where the actin-binding affinity must be optimal for accumulation. In addition, we leveraged genetic mutants to gain a molecular understanding of the mechanisms of α-actinin and filamin catch-bonding behavior. Two distinct modes of mechanoaccumulation can be observed: a fast, diffusion-based accumulation and a slower, myosin II-dependent cortical flow phase that acts on proteins with specific binding lifetimes. Finally, we uncovered cell-type- and cell-cycle-stage-specific control of the mechanosensation of myosin IIB, but not myosin IIA or IIC. Overall, these mechanoaccumulative mechanisms drive the cell's response to physical perturbation during proper tissue development and disease.
    Language English
    Publishing date 2016-06-06
    Publishing country England
    Document type Journal Article
    ZDB-ID 1071731-6
    ISSN 1879-0445 ; 0960-9822
    ISSN (online) 1879-0445
    ISSN 0960-9822
    DOI 10.1016/j.cub.2016.04.007
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: 4-Hydroxyacetophenone modulates the actomyosin cytoskeleton to reduce metastasis.

    Bryan, Darren S / Stack, Melinda / Krysztofiak, Katarzyna / Cichoń, Urszula / Thomas, Dustin G / Surcel, Alexandra / Schiffhauer, Eric S / Beckett, Michael A / Khodarev, Nikolai N / Xue, Lai / Poli, Elizabeth C / Pearson, Alexander T / Posner, Mitchell C / Robinson, Douglas N / Rock, Ronald S / Weichselbaum, Ralph R

    Proceedings of the National Academy of Sciences of the United States of America

    2020  Volume 117, Issue 36, Page(s) 22423–22429

    Abstract: Metastases are the cause of the vast majority of cancer deaths. In the metastatic process, cells migrate to the vasculature, intravasate, extravasate, and establish metastatic colonies. This pattern of spread requires the cancer cells to change shape and ...

    Abstract Metastases are the cause of the vast majority of cancer deaths. In the metastatic process, cells migrate to the vasculature, intravasate, extravasate, and establish metastatic colonies. This pattern of spread requires the cancer cells to change shape and to navigate tissue barriers. Approaches that block this mechanical program represent new therapeutic avenues. We show that 4-hydroxyacetophenone (4-HAP) inhibits colon cancer cell adhesion, invasion, and migration in vitro and reduces the metastatic burden in an in vivo model of colon cancer metastasis to the liver. Treatment with 4-HAP activates nonmuscle myosin-2C (NM2C) (
    MeSH term(s) Acetophenones/pharmacology ; Actins/metabolism ; Actomyosin/metabolism ; Animals ; Cell Adhesion/drug effects ; Cell Movement/drug effects ; Colorectal Neoplasms/metabolism ; Cytoskeleton/drug effects ; Cytoskeleton/metabolism ; Female ; HCT116 Cells ; Humans ; Mice ; Mice, Nude ; Neoplasm Metastasis/physiopathology
    Chemical Substances Acetophenones ; Actins ; Actomyosin (9013-26-7) ; 4-hydroxyacetophenone (G1L3HT4CMH)
    Language English
    Publishing date 2020-08-26
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 209104-5
    ISSN 1091-6490 ; 0027-8424
    ISSN (online) 1091-6490
    ISSN 0027-8424
    DOI 10.1073/pnas.2014639117
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article: Parallel Compression Is a Fast Low-Cost Assay for the High-Throughput Screening of Mechanosensory Cytoskeletal Proteins in Cells

    Miao, Chunguang / Schiffhauer, Eric S / Okeke, Evelyn I / Robinson, Douglas N / Luo, Tianzhi

    ACS applied materials & interfaces. 2017 Aug. 30, v. 9, no. 34

    2017  

    Abstract: ... theories, we simulated the mechanosensory accumulation of myosin II’s and quantitatively reproduced ...

    Abstract Cellular mechanosensing is critical for many biological processes, including cell differentiation, proliferation, migration, and tissue morphogenesis. The actin cytoskeletal proteins play important roles in cellular mechanosensing. Many techniques have been used to investigate the mechanosensory behaviors of these proteins. However, a fast, low-cost assay for the quantitative characterization of these proteins is still lacking. Here, we demonstrate that compression assay using agarose overlay is suitable for the high throughput screening of mechanosensory proteins in live cells while requiring minimal experimental setup. We used several well-studied myosin II mutants to assess the compression assay. On the basis of elasticity theories, we simulated the mechanosensory accumulation of myosin II’s and quantitatively reproduced the experimentally observed protein dynamics. Combining the compression assay with confocal microscopy, we monitored the polarization of myosin II oligomers at the subcellular level. The polarization was dependent on the ratio of the two principal strains of the cellular deformations. Finally, we demonstrated that this technique could be used on the investigation of other mechanosensory proteins.
    Keywords actin ; agarose ; cell differentiation ; confocal microscopy ; deformation ; morphogenesis ; mutants ; myosin ; screening
    Language English
    Dates of publication 2017-0830
    Size p. 28168-28179.
    Publishing place American Chemical Society
    Document type Article
    ISSN 1944-8252
    DOI 10.1021%2Facsami.7b04622
    Database NAL-Catalogue (AGRICOLA)

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  7. Article ; Online: Spectrin is a mechanoresponsive protein shaping fusogenic synapse architecture during myoblast fusion.

    Duan, Rui / Kim, Ji Hoon / Shilagardi, Khurts / Schiffhauer, Eric S / Lee, Donghoon M / Son, Sungmin / Li, Shuo / Thomas, Claire / Luo, Tianzhi / Fletcher, Daniel A / Robinson, Douglas N / Chen, Elizabeth H

    Nature cell biology

    2018  Volume 20, Issue 6, Page(s) 688–698

    Abstract: Spectrin is a membrane skeletal protein best known for its structural role in maintaining cell shape and protecting cells from mechanical damage. Here, we report that α/ ... ...

    Abstract Spectrin is a membrane skeletal protein best known for its structural role in maintaining cell shape and protecting cells from mechanical damage. Here, we report that α/β
    MeSH term(s) Animals ; Animals, Genetically Modified ; Cell Fusion ; Cell Line ; Cell Membrane/metabolism ; Cell Membrane/ultrastructure ; Drosophila Proteins/genetics ; Drosophila Proteins/metabolism ; Drosophila melanogaster/genetics ; Drosophila melanogaster/metabolism ; Drosophila melanogaster/ultrastructure ; Mechanotransduction, Cellular ; Membrane Fusion ; Mice ; Microscopy, Fluorescence ; Models, Biological ; Myoblasts/metabolism ; Myoblasts/ultrastructure ; Myoblasts, Skeletal/metabolism ; Spectrin/genetics ; Spectrin/metabolism ; Stress, Mechanical ; Time Factors
    Chemical Substances Drosophila Proteins ; kst protein, Drosophila ; Spectrin (12634-43-4)
    Language English
    Publishing date 2018-05-25
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S. ; Video-Audio Media
    ZDB-ID 1474722-4
    ISSN 1476-4679 ; 1465-7392
    ISSN (online) 1476-4679
    ISSN 1465-7392
    DOI 10.1038/s41556-018-0106-3
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Targeting Mechanoresponsive Proteins in Pancreatic Cancer: 4-Hydroxyacetophenone Blocks Dissemination and Invasion by Activating MYH14.

    Surcel, Alexandra / Schiffhauer, Eric S / Thomas, Dustin G / Zhu, Qingfeng / DiNapoli, Kathleen T / Herbig, Maik / Otto, Oliver / West-Foyle, Hoku / Jacobi, Angela / Kräter, Martin / Plak, Katarzyna / Guck, Jochen / Jaffee, Elizabeth M / Iglesias, Pablo A / Anders, Robert A / Robinson, Douglas N

    Cancer research

    2019  Volume 79, Issue 18, Page(s) 4665–4678

    Abstract: Metastasis is complex, involving multiple genetic, epigenetic, biochemical, and physical changes in the cancer cell and its microenvironment. Cells with metastatic potential are often characterized by altered cellular contractility and deformability, ... ...

    Abstract Metastasis is complex, involving multiple genetic, epigenetic, biochemical, and physical changes in the cancer cell and its microenvironment. Cells with metastatic potential are often characterized by altered cellular contractility and deformability, lending them the flexibility to disseminate and navigate through different microenvironments. We demonstrate that mechanoresponsiveness is a hallmark of pancreatic cancer cells. Key mechanoresponsive proteins, those that accumulate in response to mechanical stress, specifically nonmuscle myosin IIA (MYH9) and IIC (MYH14), α-actinin 4, and filamin B, were highly expressed in pancreatic cancer as compared with healthy ductal epithelia. Their less responsive sister paralogs-myosin IIB (MYH10), α-actinin 1, and filamin A-had lower expression differential or disappeared with cancer progression. We demonstrate that proteins whose cellular contributions are often overlooked because of their low abundance can have profound impact on cell architecture, behavior, and mechanics. Here, the low abundant protein MYH14 promoted metastatic behavior and could be exploited with 4-hydroxyacetophenone (4-HAP), which increased MYH14 assembly, stiffening cells. As a result, 4-HAP decreased dissemination, induced cortical actin belts in spheroids, and slowed retrograde actin flow. 4-HAP also reduced liver metastases in human pancreatic cancer-bearing nude mice. Thus, increasing MYH14 assembly overwhelms the ability of cells to polarize and invade, suggesting targeting the mechanoresponsive proteins of the actin cytoskeleton as a new strategy to improve the survival of patients with pancreatic cancer. SIGNIFICANCE: This study demonstrates that mechanoresponsive proteins become upregulated with pancreatic cancer progression and that this system of proteins can be pharmacologically targeted to inhibit the metastatic potential of pancreatic cancer cells.
    MeSH term(s) Acetophenones/pharmacology ; Actin Cytoskeleton ; Actinin/genetics ; Actinin/metabolism ; Animals ; Apoptosis ; Cell Proliferation ; Humans ; Liver Neoplasms/drug therapy ; Liver Neoplasms/metabolism ; Liver Neoplasms/secondary ; Mice ; Mice, Nude ; Myosin Heavy Chains/genetics ; Myosin Heavy Chains/metabolism ; Myosin Type II/genetics ; Myosin Type II/metabolism ; Neoplasm Invasiveness ; Pancreatic Neoplasms/drug therapy ; Pancreatic Neoplasms/metabolism ; Pancreatic Neoplasms/pathology ; Prognosis ; Tumor Cells, Cultured ; Tumor Microenvironment ; Xenograft Model Antitumor Assays
    Chemical Substances ACTN4 protein, human ; Acetophenones ; MYH14 protein, human ; Actinin (11003-00-2) ; Myosin Type II (EC 3.6.1.-) ; Myosin Heavy Chains (EC 3.6.4.1) ; 4-hydroxyacetophenone (G1L3HT4CMH)
    Language English
    Publishing date 2019-07-29
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 1432-1
    ISSN 1538-7445 ; 0008-5472
    ISSN (online) 1538-7445
    ISSN 0008-5472
    DOI 10.1158/0008-5472.CAN-18-3131
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Dual activation of CFTR and CLCN2 by lubiprostone in murine nasal epithelia.

    Schiffhauer, Eric S / Vij, Neeraj / Kovbasnjuk, Olga / Kang, Po Wei / Walker, Doug / Lee, Seakwoo / Zeitlin, Pamela L

    American journal of physiology. Lung cellular and molecular physiology

    2013  Volume 304, Issue 5, Page(s) L324–31

    Abstract: Multiple sodium and chloride channels on the apical surface of nasal epithelial cells contribute to periciliary fluid homeostasis, a function that is disrupted in patients with cystic fibrosis (CF). Among these channels is the chloride channel CLCN2, ... ...

    Abstract Multiple sodium and chloride channels on the apical surface of nasal epithelial cells contribute to periciliary fluid homeostasis, a function that is disrupted in patients with cystic fibrosis (CF). Among these channels is the chloride channel CLCN2, which has been studied as a potential alternative chloride efflux pathway in the absence of CFTR. The object of the present study was to use the nasal potential difference test (NPD) to quantify CLCN2 function in an epithelial-directed TetOn CLCN2 transgenic mouse model (TGN-K18rtTA-hCLCN2) by using the putative CLCN2 pharmacological agonist lubiprostone and peptide inhibitor GaTx2. Lubiprostone significantly increased chloride transport in the CLCN2-overexpressing mice following activation of the transgene by doxycycline. This response to lubiprostone was significantly inhibited by GaTx2 after CLCN2 activation in TGN-CLCN2 mice. Cftr(-/-) and Clc2(-/-) mice showed hyperpolarization indicative of chloride efflux in response to lubiprostone, which was fully inhibited by GaTx2 and CFTR inhibitor 172 + GlyH-101, respectively. Our study reveals lubiprostone as a pharmacological activator of both CFTR and CLCN2. Overexpression and activation of CLCN2 leads to improved mouse NPD readings, suggesting it is available as an alternative pathway for epithelial chloride secretion in murine airways. The utilization of CLCN2 as an alternative chloride efflux channel could provide clinical benefit to patients with CF, especially if the pharmacological activator is administered as an aerosol.
    MeSH term(s) Alprostadil/analogs & derivatives ; Alprostadil/pharmacology ; Animals ; Chloride Channels/biosynthesis ; Chloride Channels/genetics ; Chloride Channels/metabolism ; Cystic Fibrosis/metabolism ; Cystic Fibrosis Transmembrane Conductance Regulator/biosynthesis ; Cystic Fibrosis Transmembrane Conductance Regulator/genetics ; Cystic Fibrosis Transmembrane Conductance Regulator/metabolism ; Genotype ; Ion Transport/drug effects ; Lubiprostone ; Membrane Potentials ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Nasal Mucosa/drug effects ; Nasal Mucosa/metabolism ; Scorpion Venoms/pharmacology
    Chemical Substances Chloride Channels ; ClC-2 chloride channels ; GaTx2 protein, Leiurus quinquestriatus hebraeus ; Scorpion Venoms ; Cystic Fibrosis Transmembrane Conductance Regulator (126880-72-6) ; Lubiprostone (7662KG2R6K) ; Alprostadil (F5TD010360)
    Language English
    Publishing date 2013-01-11
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 1013184-x
    ISSN 1522-1504 ; 1040-0605
    ISSN (online) 1522-1504
    ISSN 1040-0605
    DOI 10.1152/ajplung.00277.2012
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Interference with ubiquitination in CFTR modifies stability of core glycosylated and cell surface pools.

    Lee, Seakwoo / Henderson, Mark J / Schiffhauer, Eric / Despanie, Jordan / Henry, Katherine / Kang, Po Wei / Walker, Douglas / McClure, Michelle L / Wilson, Landon / Sorscher, Eric J / Zeitlin, Pamela L

    Molecular and cellular biology

    2014  Volume 34, Issue 14, Page(s) 2554–2565

    Abstract: It is recognized that both wild-type and mutant CFTR proteins undergo ubiquitination at multiple lysines in the proteins and in one or more subcellular locations. We hypothesized that ubiquitin is added to specific sites in wild-type CFTR to stabilize it ...

    Abstract It is recognized that both wild-type and mutant CFTR proteins undergo ubiquitination at multiple lysines in the proteins and in one or more subcellular locations. We hypothesized that ubiquitin is added to specific sites in wild-type CFTR to stabilize it and at other sites to signal for proteolysis. Mass spectrometric analysis of wild-type CFTR identified ubiquitinated lysines 68, 710, 716, 1041, and 1080. We demonstrate that the ubiquitinated K710, K716, and K1041 residues stabilize wild-type CFTR, protecting it from proteolysis. The polyubiquitin linkage is predominantly K63. N-tail mutants, K14R and K68R, lead to increased mature band CCFTR, which can be augmented by proteasomal (but not lysosomal) inhibition, allowing trafficking to the surface. The amount of CFTR in the K1041R mutant was drastically reduced and consisted of bands A/B, suggesting that the site in transmembrane 10 (TM10) was critical to further processing beyond the proteasome. The K1218R mutant increases total and cell surface CFTR, which is further accumulated by proteasomal and lysosomal inhibition. Thus, ubiquitination at residue 1218 may destabilize wild-type CFTR in both the endoplasmic reticulum (ER) and recycling pools. Small molecules targeting the region of residue 1218 to block ubiquitination or to preserving structure at residues 710 to 716 might be protein sparing for some forms of cystic fibrosis.
    MeSH term(s) Cell Line ; Cell Membrane/metabolism ; Cystic Fibrosis/genetics ; Cystic Fibrosis/metabolism ; Cystic Fibrosis/pathology ; Cystic Fibrosis Transmembrane Conductance Regulator/genetics ; Cystic Fibrosis Transmembrane Conductance Regulator/metabolism ; Endoplasmic Reticulum/metabolism ; HEK293 Cells ; Humans ; Lysine/metabolism ; Mass Spectrometry ; Models, Molecular ; Mutation ; Proteasome Endopeptidase Complex/metabolism ; Protein Conformation ; Protein Processing, Post-Translational ; Protein Stability ; Protein Structure, Tertiary ; Protein Transport ; Proteolysis ; Ubiquitin/metabolism ; Ubiquitination
    Chemical Substances CFTR protein, human ; Ubiquitin ; Cystic Fibrosis Transmembrane Conductance Regulator (126880-72-6) ; Proteasome Endopeptidase Complex (EC 3.4.25.1) ; Lysine (K3Z4F929H6)
    Language English
    Publishing date 2014-04-28
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 779397-2
    ISSN 1098-5549 ; 0270-7306
    ISSN (online) 1098-5549
    ISSN 0270-7306
    DOI 10.1128/MCB.01042-13
    Database MEDical Literature Analysis and Retrieval System OnLINE

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